Publications by authors named "Jun Cao"

1,001 Publications

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Perioperative Exercise Intention and Influencing Factors: A Multi-Centered Cross-Sectional Study.

Front Public Health 2021 20;9:653055. Epub 2021 May 20.

Department of Anesthesiology, Youyang Hospital, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

This study aimed to evaluate the level and factors affecting the perioperative exercise intention in China. This study was a cross-sectional survey in Southwest China. Four hundred and ninety nine participants were randomly sampled in eight medical centers from November 23, 2020 to November 27, 2020. The survey included sociodemographic information and a 24-item modified questionnaire, which aimed to evaluate the attitude toward daily exercise, perception of perioperative exercise, social support and the perioperative exercise intention. A multivariable linear regression model was used to evaluate the effect of different items on the patients' intention for perioperative exercise. A total of 523 responses (95.09%) were collected and 499 (95.41%) were analyzed. The level of exercise intention of the patients during the perioperative period was: 14.83% planned to exercise every day in the hospital, 21.04% planned to exercise every other day, and 35.87% planned to exercise every week. Intensity of daily exercise ( = 0.016), positive attitude of daily exercise ( < 0.001), positive attitude of perioperative exercise ( < 0.001) and social support ( < 0.001) were positively associated with the intention for perioperative exercise. Female ( = 0.012), non-tertiary center ( = 0.011), and preoperative anxiety ( = 0.023) was negatively associated with it. The intention for perioperative exercise was low in Southwest China. The authors aimed to relieve preoperative anxiety, promote the education of perioperative exercise, design perioperative exercise programs, and provide more social support from medical staff and family for inpatients undergoing elective surgery.
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http://dx.doi.org/10.3389/fpubh.2021.653055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172588PMC
June 2021

CXCR3 alleviates renal ischemia‑reperfusion injury via increase of Tregs.

Mol Med Rep 2021 Jul 3;24(1). Epub 2021 Jun 3.

Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.

Increasing evidence has demonstrated that regulatory T cells (Tregs) suppress innate immunity, as well as protect the kidneys from ischemia‑reperfusion injury (IRI) and offer a potentially effective strategy to prevent or alleviate renal IRI. The present study explored whether C‑X‑C motif chemokine receptor 3 (CXCR3) alleviated renal IRI by increasing Tregs. Male C57BL/6J mice were divided into sham‑surgery, IRI, CXCR3 overexpression (OE‑CXCR3)+IRI, PC61+IRI and OE‑CXCR3+PC61+IRI groups. Histopathological examination of the kidney was carried out using hematoxylin‑eosin and Masson staining. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Blood and kidney levels of IL‑6, TNF‑α, C‑C motif chemokine ligand (CCL)‑2 and IL‑10 were detected by ELISA and western blotting. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) and malondialdehyde (MDA) in kidney tissues were also measured to assess oxidative stress. The population of Tregs in the kidney was assessed using flow cytometry. The results demonstrated that administration of OE‑CXCR3 to IRI mice significantly decreased the levels of Scr, BUN, IL‑6, TNF‑α, CCL‑2 and MDA, increased the levels of IL‑10, SOD and GSH‑Px, and mitigated the morphologic injury and fibrosis induced by IR compared with the IRI group. In addition, administration of OE‑CXCR3 induced significant reductions in the expression levels of fibrosis‑related markers, including fibronectin and type IV collagen, and increased the number of Tregs. These roles of OE‑CXCR3 were significantly neutralized following deletion of Tregs with PC61 (anti‑CD25 antibody). Together, the present study demonstrated that injection of OE‑CXCR3 lentiviral vectors into animal models can alleviate renal IRI by increasing the number of Tregs. The results may be a promising approach for the treatment of renal IRI.
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http://dx.doi.org/10.3892/mmr.2021.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170869PMC
July 2021

Correlation and integration of circulating miRNA and peripheral whole blood gene expression profiles in patients with venous thromboembolism.

Bioengineered 2021 Dec;12(1):2352-2363

Emergency and Acute Critical Care Department, Huashan Hospital North, Fudan University, Shanghai, China.

The main aim of this work was to evaluate differential expression and biological functions of circulating miRNA and whole peripheral blood (PB) genes in patients affected by venous thromboembolism (VTE) and in healthy subjects. Circulating miRNA sequences and PB expression profiles were obtained from GEO datasets. Ten miRNAs with the most significant differential expression rate (dif-miRNA) were subjected to miRbase to confirm their identity. Dif-miRNA targets were predicted by TargetScan and aligned with differentially expressed genes to obtain overlapping co-genes. Biological functions of co-genes were analyzed by Gene Ontology and KEGG analysis. Interaction network of dif-miRNAs, co-genes, and their downstream pathways were studied by analyzing protein-protein interaction (PPI) clusters (STRING) and determining the crucial hubs (Cytoscape).MiR-522-3p and miR-134 dif-miRNAs are involved in protein translation and apoptosis by regulating their respective co-genes in PB. Co-genes are present in nucleolus and extracellular exosomes and are involved in oxidative phosphorylation and ribosome/poly(A)-RNA organization. The predicted PPI network covered 107 clustered genes and 220 marginal joints, where ten hub genes participating in PPIs were found. All these hub genes were down-regulated in VTE patients. Our study identifies new miRNAs as potential biological markers and therapeutic targets for VTE.
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http://dx.doi.org/10.1080/21655979.2021.1935401DOI Listing
December 2021

In vitro inhibition of human UDP-glucuronosyltransferase (UGT) 1A1 by osimertinib, and prediction of in vivo drug-drug interactions.

Toxicol Lett 2021 May 24;348:10-17. Epub 2021 May 24.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 124221, China. Electronic address:

Osimertinib is the only third-generation epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) approved by Food and Drug Administration (FDA). This study aimed to know the inhibitory effect of osimertinib on human UDP-glucosyltransferases (UGTs) and human liver microsomes (HLMs), as well as to identify its potential to cause drug-drug interaction (DDI) arising from the modulation of UGT activity. High inhibitory effect of osimertinib was shown towards UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A10, 2B7 and 2B15. Especially, osimertinib exhibited competitive inhibition against UGT1A1 with a K of 0.87 ± 0.12 μM. It also noncompetitively inhibited SN-38 glucuronidation in pooled HLMs with a K of 3.32 ± 0.25 μM. Results from quantitative prediction study indicated that osimertinib administered at 80 mg/day may result in a 4.83 % increase in the AUC of drugs mainly metabolized by UGT1A1, implying low risk of DDI via liver metabolism. However, the ratios of [I]/K are much higher than 11 in HLMs and recombinant UGT1A1, indicating a risk for interaction in intestine. The effects of osimertinib on intestinal UGT should be paid more attention on to avoid unnecessary clinical DDI risks.
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http://dx.doi.org/10.1016/j.toxlet.2021.05.004DOI Listing
May 2021

Comparison of the drug-drug interactions potential of ibrutinib and acalabrutinib via inhibition of UDP-glucuronosyltransferase.

Toxicol Appl Pharmacol 2021 May 24;424:115595. Epub 2021 May 24.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, China. Electronic address:

Ibrutinib and acalabrutinib are two Bruton's tyrosine kinase (BTK) inhibitors which have gained Food and Drug Administration (FDA) approval for the treatment of various B cell malignancies. Herein, we investigated the effects of the two drugs on UDP-glucuronosyltransferase (UGT) activities to evaluate their potential risk for drug-drug interactions (DDIs) via UGT inhibition. Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a K value of 0.90 ± 0.03 μM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with K values of 0.88 ± 0.03 μM and 2.52 ± 0.23 μM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms. DDI risk prediction suggested that the inhibition against UGT1A1 and UGT1A3 by ibrutinib might bring a potential DDIs risk, while acalabrutinib was unlikely to trigger clinically significant UGT-mediated DDIs due to its weak effects. Our study raises an alarm bell about potential DDI risk associated with ibrutinib, however, the extrapolation from in vitro data to in vivo drug interactions should be taken with caution, and additional systemic study is needed.
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http://dx.doi.org/10.1016/j.taap.2021.115595DOI Listing
May 2021

Synthesis of a biotinylated heptose 1,7-bisphosphate analogue, a probe to study immunity and inflammation.

Org Biomol Chem 2021 Jun;19(22):4943-4948

University of Namur (UNamur), NARILIS, Department of Chemistry, rue de Bruxelles 61, 5000 Namur, Belgium.

d-glycero-d-manno-Heptose-1β,7-bisphosphate (HBP) is a bacterial metabolite that can induce a TIFA-dependent innate immune response in mammals. It was recently discovered that after HBP enters into the cytoplasm of the host cell, it is transformed into ADP-heptose-7-phosphate, which then leads to ALPK1-TIFA-dependent inflammatory response. In order to provide a molecular tool allowing the discovery of the proteins involved in this novel inflammatory pathway, we designed and synthesized a biotinylated analogue of HBP. This chemical probe displays an anomeric β-phosphate and a phosphonate at the 7-position, and a d-configured 6-position to which is attached the biotin moiety. To do so, different synthetic strategies were explored and described in this report. Moreover, we demonstrated that the biotinylated version of HBP is still biologically active and can activate the NF-κB pathway in HEK293T cells.
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http://dx.doi.org/10.1039/d1ob00790dDOI Listing
June 2021

Differential prognostic implications of gastric adenocarcinoma based on Lauren's classification: a Surveillance, Epidemiology, and End Results (SEER)-based cohort study.

Ann Transl Med 2021 Apr;9(8):646

Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

Background: Our study aims to analyze the association between Lauren's classification and gastric adenocarcinoma prognosis using comprehensive statistical analyses.

Methods: According to the selection criteria, patients were included from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression, propensity score matching, and a multivariate competing risk model were used to investigate the association between Lauren's classification and prognosis. Subgroup analysis was used to investigate the role of confounding factors on the association between Lauren types and prognosis.

Results: After exclusion, a total of 20,218 patients from the SEER database were included, with 14,374 intestinal types and 5,844 diffuse types. The univariate Cox regression analysis revealed that the diffuse type had a poorer cancer-specific survival (CSS) rate [hazard ratio (HR), 1.44; 95% confidence interval (CI), 1.38-1.50]. After adjusting for confounding variables, the diffuse type also showed a higher risk of cancer-specific death (HR, 1.20; 95% CI, 1.15-1.20). Sensitivity analysis showed that after propensity score matching, the diffuse type had a poorer CSS rate (HR, 1.23; 95% CI, 1.10-1.36), and the competing risk model further validated these results [subdistribution HR (SHR), 1.32; 95% CI, 1.23-1.41]. Moreover, subgroup analysis demonstrated stable results in the subgroups, except for patients with T1 stage (HR, 1.06; 95% CI, 0.87-1.28) and a tumor size <2 cm (HR, 1.00; 95% CI, 0.83-1.21).

Conclusions: Diffuse-type gastric adenocarcinoma had an overall poorer prognosis compared to the intestinal type. However, in patients with T1 stage and tumor size <2 cm, the diffuse type had a comparable survival rate with the intestinal type.
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http://dx.doi.org/10.21037/atm-20-7953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106066PMC
April 2021

A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase.

Nat Microbiol 2021 Jun 6;6(6):806-817. Epub 2021 May 6.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field.
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http://dx.doi.org/10.1038/s41564-021-00899-8DOI Listing
June 2021

A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase.

Nat Microbiol 2021 Jun 6;6(6):806-817. Epub 2021 May 6.

CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field.
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http://dx.doi.org/10.1038/s41564-021-00899-8DOI Listing
June 2021

NR4A1 knockdown confers hepatoprotection against ischaemia-reperfusion injury by suppressing TGFβ1 via inhibition of CYR61/NF-κB in mouse hepatocytes.

J Cell Mol Med 2021 Jun 3;25(11):5099-5112. Epub 2021 May 3.

Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Nuclear receptor subfamily 4, group A, member 1 (NR4A1) can aggravate ischaemia-reperfusion (I/R) injury in the heart, kidney and brain. Thus, the present study aimed to unravel the role of NR4A1 on hepatic I/R injury. For this purpose, the mouse hepatic I/R model and H/R-exposed mouse hepatocytes model were established to stimulate the hepatic and hepatocellular damage. Then, the levels of ALT and AST as well as TNF-α and IL-1β expression were measured in the mouse serum and supernatant of hepatocyte s, respectively. Thereafter, we quantified the levels of NR4A1, CYR61, NF-kB p65 and TGFβ1 under pathological conditions, and their interactions were analysed using ChIP and dual-luciferase reporter gene assays. The in vivo and in vitro effects of NR4A1, CYR61, NF-kB p65 and TGFβ1 on I/R-induced hepatic and H/R-induced hepatocellular damage were evaluated using gain- and loss-of-function approaches. NR4A1 was up-regulated in the hepatic tissues of I/R-operated mice and in H/R-treated hepatocytes. Silencing NR4A1 relieved the I/R-induced hepatic injury, as supported by suppression of ALT and AST as well as TNF-α and IL-1β. Meanwhile, NR4A1 knockdown attenuated the H/R-induced hepatocellular damage by inhibiting the apoptosis of hepatocyte s. Moreover, we also found that NR4A1 up-regulated the expression of CYR61 which resulted in the activation of the NF-κB signalling pathway, thereby enhancing the transcription of TGFβ1, which was validated to be the mechanism underlying the contributory role of NR4A1 in hepatic I/R injury. Taken together, NR4A1 silencing reduced the expression of CYR61/NF-κB/TGFβ1, thereby relieving the hepatic I/R injury.
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http://dx.doi.org/10.1111/jcmm.16493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178266PMC
June 2021

Long non-coding RNA CYTOR regulates proliferation and metastasis of colon cancer cells through regulating miRNA-105/PTEN axis.

Int J Clin Exp Pathol 2021 15;14(4):434-443. Epub 2021 Apr 15.

Department of General Surgery, General Hospital of Central Theater Command of PLA Wuhan 430071, Hubei, China.

Colon cancer is a common malignancy, and its incidence and mortality have been increasing in recent years. This study aims to explore the regulation of long non-coding RNA CYTOR on proliferation and metastasis of colon cancer cells through miRNA-105/PTEN axis. Real-time quantitative PCR (qRT-PCR) disclosed that expression of CYTOR was significantly decreased in colon cancer tissues, compared with that of adjacent normal tissues, while miRNA-105 was significantly increased. Correlation study found that CYTOR was negatively correlated with miR-105. The proliferation, migration, and invasion rates of the LoVo cells with highly expressed CYTOR were significantly slower. miR-105 mimic could suppress the decrease in proliferation, migration, and invasion rates of colon cancer cells caused by overexpression of CYTOR. Additionally, the proliferation, migration, and invasion rates of the LoVo cells in miR-105 inhibition group were significantly slower. The Starbase database predicted the targeting of miR-105 by CYTOR, and qRT-PCR and dual luciferase reporter gene method were used to verify the targeting relationship of CYTOR and miRNA-105/PTEN axis. In conclusion, CYTOR can inhibit the proliferation and metastasis of colon cancer cells through targeted inhibition of the miR-105/PTEN axis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085819PMC
April 2021

Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient.

Breast Cancer Res 2021 May 1;23(1):53. Epub 2021 May 1.

State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.

We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.
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http://dx.doi.org/10.1186/s13058-021-01428-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088670PMC
May 2021

Anti-proliferative cassane-type diterpenoids from the seeds of .

Nat Prod Res 2020 Dec 1:1-10. Epub 2020 Dec 1.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.

The seeds of Hance have shown anti-tumor potential, while the chemical principle is still unknown. In a search for anti-tumor compounds, six new cassane-type diterpenoids, 12-demethylcaesalpin G (), caesalpinolide H (), 12-demethylcaesalpin H (), caesalpinolide J (), 12--ethyl neocaesalpin B (), and 3-deacetyldecapetpene B (), were isolated from the seeds of Hance, along with fifteen known analogues. The structures of the new compounds were established by means of spectroscopic techniques (NMR, HRESIMS and IR). The absolute configurations of the new compounds were determined by their ECD spectra. All of the new compounds were tested for their anti-proliferative activity against human lung cancer A549 cells, breast cancer MCF-7 cells, and ovarian cancer HEY cells. The results indicated that only compound displayed moderate cytotoxicity against three cancer cell lines. Thus, the opening of furan ring in cassane-type diterpenoids might enhance the cytotoxic activity.
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http://dx.doi.org/10.1080/14786419.2020.1853729DOI Listing
December 2020

A Revised Hilbert-Huang Transformation to Track Non-Stationary Association of Electroencephalography Signals.

IEEE Trans Neural Syst Rehabil Eng 2021 7;29:841-851. Epub 2021 May 7.

The time-varying cross-spectrum method has been used to effectively study transient and dynamic brain functional connectivity between non-stationary electroencephalography (EEG) signals. Wavelet-based cross-spectrum is one of the most widely implemented methods, but it is limited by the spectral leakage caused by the finite length of the basic function that impacts the time and frequency resolutions. This paper proposes a new time-frequency brain functional connectivity analysis framework to track the non-stationary association of two EEG signals based on a Revised Hilbert-Huang Transform (RHHT). The framework can estimate the cross-spectrum of decomposed components of EEG, followed by a surrogate significance test. The results of two simulation examples demonstrate that, within a certain statistical confidence level, the proposed framework outperforms the wavelet-based method in terms of accuracy and time-frequency resolution. A case study on classifying epileptic patients and healthy controls using interictal seizure-free EEG data is also presented. The result suggests that the proposed method has the potential to better differentiate these two groups benefiting from the enhanced measure of dynamic time-frequency association.
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http://dx.doi.org/10.1109/TNSRE.2021.3076311DOI Listing
May 2021

The Architectural Factor HMGB1 Is Involved in Genome Organization in the Human Malaria Parasite Plasmodium falciparum.

mBio 2021 04 27;12(2). Epub 2021 Apr 27.

Unit of Molecular Parasitology, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China

The three-dimensional (3D) genome organization plays a critical role in the regulation of gene expression in eukaryotic organisms. In the unicellular malaria parasite , the high-order chromosome organization has emerged as an important epigenetic pathway mediating gene expression, particularly for virulence genes, but the related architectural factors and underlying mechanism remain elusive. Herein, we have identified the high-mobility-group protein HMGB1 as a critical architectural factor for maintenance of genome organization in Genome-wide occupancy analysis (chromatin immunoprecipitation sequencing [ChIP-seq]) shows that the HMGB1 protein is recruited mainly to centromeric regions likely via a DNA-binding-independent pathway. Chromosome conformation capture coupled with next-generation sequencing (Hi-C-seq) and 3D modeling analysis show that the loss of HMGB1 disrupts the integrity of centromere/telomere-based chromosome organization accompanied with diminished interaction frequency among centromere clusters. This triggers local chromatin alteration and dysregulated gene expression. Notably, the entire repertoire of the primary virulence genes () was completely silenced in the absence of HMGB1 (PfHMGB1). Furthermore, the disrupted nuclear organization was reconstituted by complementation of HMGB1, thereby rescuing the mutually exclusive expression of the gene family. Collectively, these data demonstrate that the architectural factor HMGB1 is associated with gene expression via mediating the high-order structure of genome organization. This finding not only contributes better understanding of the epigenetic regulation of gene expression but may also provide novel targets for antimalarial strategies. Malaria remains a major public health and economic burden currently. The mutually exclusive expression of the virulence genes is associated with the pathogenesis and immune evasion of human malaria parasites in the host. The nuclear architecture provides a well-organized environment for differential gene expression in the nucleus, but the underlying mechanism remains largely unknown. In this study, we have identified the highly conserved high-mobility-group protein HMGB1 as a key architecture regulator involved in virulence gene expression by establishing high-order genome organization in the nucleus of Mechanistic investigation revealed that the specific interaction of HMGB1 and centromeres constructed the precisely organized nuclear architecture, which coordinated with local chromatin structure to control the singular expression of virulence genes. Hence, this protein appears to be a critical architectural regulator for the pathogenesis of malaria infection and may be a new target for the development of an intervention strategy against malaria.
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http://dx.doi.org/10.1128/mBio.00148-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092211PMC
April 2021

Spin-induced linear polarization of photoluminescence in antiferromagnetic van der Waals crystals.

Nat Mater 2021 Apr 26. Epub 2021 Apr 26.

Department of Chemistry, Boston University, Boston, MA, USA.

Antiferromagnets are promising components for spintronics due to their terahertz resonance, multilevel states and absence of stray fields. However, the zero net magnetic moment of antiferromagnets makes the detection of the antiferromagnetic order and the investigation of fundamental spin properties notoriously difficult. Here, we report an optical detection of Néel vector orientation through an ultra-sharp photoluminescence in the van der Waals antiferromagnet NiPS from bulk to atomically thin flakes. The strong correlation between spin flipping and electric dipole oscillator results in a linear polarization of the sharp emission, which aligns perpendicular to the spin orientation in the crystal. By applying an in-plane magnetic field, we achieve manipulation of the photoluminescence polarization. This correlation between emitted photons and spins in layered magnets provides routes for investigating magneto-optics in two-dimensional materials, and hence opens a path for developing opto-spintronic devices and antiferromagnet-based quantum information technologies.
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http://dx.doi.org/10.1038/s41563-021-00968-7DOI Listing
April 2021

Insights into the co-doping effect of Fe and Zr on the anti-K performance of CeTiO catalyst for NH-SCR reaction.

J Hazard Mater 2021 Apr 8;416:125821. Epub 2021 Apr 8.

Research Center for Atmospheric Environment, Key Laboratory of Reservoir Aquatic Environment of CAS, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing 400714, PR China; College of Resources and Environment, Chongqing School, University of Chinese Academy of Sciences (UCAS Chongqing), Chongqing 400714, PR China; School of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, PR China.

A novel K-resistant Fe and Zr co-doped CeTiO catalyst was first prepared by co-precipitation method for the ammonia-selective catalytic reduction (NH-SCR) of NO. On the premise of retaining the outstanding catalytic activity of CeTiO catalyst, Fe and Zr co-doping efficiently improves its K-resistance with superior NO conversion up to 84% after K-poisoning. Specially, the grain growth during the second calcination after K poisoning is successfully inhibited by Fe and Zr co-doping. Consequently, the large specific surface area with increased acid sites and efficiently retained reducibility over K-poisoned FeZrCeTiO catalyst are realized, which prompt NH activation and NO oxidation, further benefit NH-SCR. Besides, NH-SCR reaction over CeTiO and FeZrCeTiO catalysts follows a possible L-H mechanism, and K-poisoning makes no change to it. Finally, a reasonable anti-K poisoning mechanism of FeZrCeTiO catalyst is proposed: the excellent K-resistance is attributed to part of Fe and Zr are sacrificed to form Fe-O-K and Zr-O-K species protecting the active site Ce-O-Ti from K-poisoning, as well as the additional reducibility and surface acidity brought from Fe-O species with Zr prompting its uniform distribution.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125821DOI Listing
April 2021

Research supporting malaria control and elimination in China over four decades: a bibliometric analysis of academic articles published in chinese from 1980 to 2019.

Malar J 2021 Mar 20;20(1):158. Epub 2021 Mar 20.

Key Lab of Health Technology Assessment, School of Public Health, National Health Commission, Fudan University, 200433, Shanghai, China.

Background: China has accumulated considerable experience in malaria control and elimination over the past decades. Many research papers have been published in Chinese journals. This study intends to describe the development and experience of malaria control and elimination in China by quantitatively analysing relevant research using a bibliometric analysis.

Methods: A long-term, multistage bibliometric analysis was performed. Research articles published in Chinese journals from 1980 to 2019 were retrieved from the Wanfang and China National Knowledge Infrastructure (CNKI) databases. Year of publication, journal name and keywords were extracted by the Bibliographic Items Co-occurrence Matrix Builder (BICOMB). The K/A ratio (the frequency of a keyword among the total number of articles within a certain period) was considered an indicator of the popularity of a keyword in different decades. VOSviewer software was used to construct keyword co-occurrence network maps.

Results: A total of 16,290 articles were included. The overall number of articles continually increased. However, the number of articles published in the last three years decreased. There were two kinds of keyword frequency trends among the different decades. The K/A ratio of the keyword 'Plasmodium falciparum' decreased (17.05 in the 1980s, 13.04% in the 1990s, 9.86 in the 2000s, 5.28 in the 2010s), but those of 'imported case' and 'surveillance' increased. Drug resistance has been a continuous concern. The keyword co-occurrence network maps showed that the themes of malaria research diversified, and the degree of multidisciplinary cooperation gradually increased.

Conclusions: This bibliometric analysis revealed the trends in malaria research in China over the past 40 years. The results suggest emphasis on investigation, multidisciplinary participation and drug resistance by researchers and policymakers in malaria epidemic areas. The results also provide domestic experts with qualitative evidence of China's experience in malaria control and elimination.
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http://dx.doi.org/10.1186/s12936-021-03698-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980574PMC
March 2021

Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway.

J Pharm Pharmacol 2021 Jun;73(7):916-921

Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China.

Objectives: Acute lung injury (ALI) is the major complication of sepsis, and no effective treatment is available now. Recently, rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts a potential role on ALI with anti-inflammation, and antioxidant properties. However, there is still no evidence on its protective effect on cell apoptosis in sepsis. Here, we investigated the protective effect of RA in septic-associated mortality and lung injury based on apoptosis.

Methods: Male C57BL/6 mice were administered with lipopolysaccharide (LPS) (15 mg/kg, ip) to establish ALI mice model. Preteatment of RA (20 or 40 mg/kg, ip) was performed once daily for five consecutive days. The mortality was monitored for seven days after injection of LPS.

Key Findings: RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury. Meanwhile, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity. Furthermore, RA pretreatment significantly inhibited lung cell apoptosis, as well as decreased p53 level in sepsis mice. Finally, the LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment.

Conclusions: These findings indicated that RA could be beneficial to septic-associated lung injury through anti-apoptosis effect.
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http://dx.doi.org/10.1093/jpp/rgaa033DOI Listing
June 2021

Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway.

J Pharm Pharmacol 2021 Jun;73(7):916-921

Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China.

Objectives: Acute lung injury (ALI) is the major complication of sepsis, and no effective treatment is available now. Recently, rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts a potential role on ALI with anti-inflammation, and antioxidant properties. However, there is still no evidence on its protective effect on cell apoptosis in sepsis. Here, we investigated the protective effect of RA in septic-associated mortality and lung injury based on apoptosis.

Methods: Male C57BL/6 mice were administered with lipopolysaccharide (LPS) (15 mg/kg, ip) to establish ALI mice model. Preteatment of RA (20 or 40 mg/kg, ip) was performed once daily for five consecutive days. The mortality was monitored for seven days after injection of LPS.

Key Findings: RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury. Meanwhile, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity. Furthermore, RA pretreatment significantly inhibited lung cell apoptosis, as well as decreased p53 level in sepsis mice. Finally, the LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment.

Conclusions: These findings indicated that RA could be beneficial to septic-associated lung injury through anti-apoptosis effect.
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http://dx.doi.org/10.1093/jpp/rgaa033DOI Listing
June 2021

Full-Length Transcriptome Analysis of by Single-Molecule Long-Read Sequencing.

Front Cell Infect Microbiol 2021 23;11:631545. Epub 2021 Feb 23.

Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China.

Malaria, an infectious disease caused by parasites, still accounts for amounts of deaths annually in last decades. Despite the significance of as a model organism of malaria parasites, our understanding of gene expression of this parasite remains largely elusive since lots of progress on its genome and transcriptome are based on assembly with short sequencing reads. Herein, we report the new version of transcriptome dataset containing all full-length transcripts over the whole asexual blood stages by adopting a full-length sequencing approach with optimized experimental conditions of cDNA library preparation. We have identified a total of 393 alternative splicing (AS) events, 3,623 long non-coding RNAs (lncRNAs), 1,555 alternative polyadenylation (APA) events, 57 transcription factors (TF), 1,721 fusion transcripts in . Furthermore, the shotgun proteome was performed to validate the full-length transcriptome of . More importantly, integration of full-length transcriptomic and proteomic data identified 160 novel small proteins in lncRNA regions. Collectively, this full-length transcriptome dataset with high quality and accuracy and the shotgun proteome analyses shed light on the complex gene expression in malaria parasites and provide a valuable resource for related functional and mechanistic researches on genes.
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http://dx.doi.org/10.3389/fcimb.2021.631545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942025PMC
February 2021

Flexible and high-performance electrochromic devices enabled by self-assembled 2D TiO/MXene heterostructures.

Nat Commun 2021 Mar 11;12(1):1587. Epub 2021 Mar 11.

Department of Chemistry, Boston University, Boston, MA, USA.

Transition metal oxides (TMOs) are promising electrochromic (EC) materials for applications such as smart windows and displays, yet the challenge still exists to achieve good flexibility, high coloration efficiency and fast response simultaneously. MXenes (e.g. TiCT) and their derived TMOs (e.g. 2D TiO) are good candidates for high-performance and flexible EC devices because of their 2D nature and the possibility of assembling them into loosely networked structures. Here we demonstrate flexible, fast, and high-coloration-efficiency EC devices based on self-assembled 2D TiO/TiCT heterostructures, with the TiCT layer as the transparent electrode, and the 2D TiO layer as the EC layer. Benefiting from the well-balanced porosity and connectivity of these assembled nanometer-thick heterostructures, they present fast and efficient ion and electron transport, as well as superior mechanical and electrochemical stability. We further demonstrate large-area flexible devices which could potentially be integrated onto curved and flexible surfaces for future ubiquitous electronics.
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http://dx.doi.org/10.1038/s41467-021-21852-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952574PMC
March 2021

Corrigendum to "CD147 depletion down-regulates matrix metalloproteinase-11, vascular endothelial growth factor-A expression and the lymphatic metastasis potential of murine hepatocarcinoma Hca-F cells" [Int. J. Biochem. Cell Biol. 39 (2007) 2135-2142].

Int J Biochem Cell Biol 2021 Jun 5;135:105947. Epub 2021 Mar 5.

Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 465 Zhongshan Road, Dalian 116027, Liaoning Province, China. Electronic address:

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http://dx.doi.org/10.1016/j.biocel.2021.105947DOI Listing
June 2021

Sclerotinia Stem Rot Resistance in Rapeseed: Recent Progress and Future Prospects.

J Agric Food Chem 2021 Mar 5;69(10):2965-2978. Epub 2021 Mar 5.

School of Life Sciences, Jiangsu University, Zhenjiang, China.

Sclerotinia stem rot (SSR) of rapeseed (), caused by the soil-borne fungus , is one of the main diseases seriously affecting the yield and oil quality of infected rapeseed crops. The complexity of the inheritance of resistance and of the interaction mechanisms between rapeseed and limits resistance gene identification and molecular breeding. In this review, the latest progress of research into resistance to SSR in is summarized from the following three directions: the pathogenesis mechanisms of , the resistance mechanisms of toward , and rapeseed breeding for resistance to SSR. This review aims to provide a theoretical basis and useful reference for analyzing the mechanism of the interaction between and , searching for gene loci associated with the resistance response, and for achieving disease-resistance genetic manipulation and molecular design breeding in rapeseed.
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http://dx.doi.org/10.1021/acs.jafc.0c07351DOI Listing
March 2021

The crosstalk between mitochondrial dysfunction and endoplasmic reticulum stress promoted ATF4-mediated mitophagy induced by hexavalent chromium.

Environ Toxicol 2021 Jun 2;36(6):1162-1172. Epub 2021 Mar 2.

Department of Occupational and Environmental Health, Dalian Medical University, Dalian, China.

Chromium (Cr) compounds are markedly toxic and carcinogenic. Previously, we found that Cr (VI) induced autophagy in A549 cells. Here, the effect of mitochondrial dysfunction and endoplasmic reticulum (ER) stress on inducing mitophagy was investigated in both A549 and H1299 cells. Exposure to Cr (VI) for 6 h significantly enhanced reactive oxygen species (ROS) production and reduced mitochondrial membrane potential (MMP). Transmission electron microscopy showed that Cr (VI) induced mitochondrial morphological changes, such as, mitochondrial swelling and vacuolization. The elevated expression of GRP78 and p-PERK suggested that Cr (VI) resulted in ER stress. Both mitochondrial dysfunction and ER stress played an important role in Cr (VI)-induced mitophagy, as the mitochondrial function inhibitor, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) induced PINK1 and PARK2 and increased the expression of GRP78 and p-PERK while the levels of Cr (VI)-induced PINK1, PARK2, LC3-II were reduced after ER stress inhibitor, phenylbutyric acid (4PBA) pretreatment. When A549 cells were treated with CCCP and 4-PBA simultaneously, CCCP-induced expressions of PINK1, PARK2 and LC3-II decreased significantly compared with that of only CCCP-treated cells, indicating that there was a crosstalk between mitochondria and ER in inducing mitophagy. Additionally, the crosstalk between mitochondrial dysfunction and ER stress modulated the expression of Cr (VI)-induced ATF4, which resulted in mitophagy. Collectively, our data demonstrated that Cr (VI)-induced mitophagy mediated by ATF4 via the crosstalk between ER stress and mitochondrial dysfunction.
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http://dx.doi.org/10.1002/tox.23115DOI Listing
June 2021

Ultrasensitive Chemodynamic Therapy: Bimetallic Peroxide Triggers High pH-Activated, Synergistic Effect/H O Self-Supply-Mediated Cascade Fenton Chemistry.

Adv Healthc Mater 2021 05 28;10(9):e2002126. Epub 2021 Feb 28.

Institute of Engineering Ceramics, School of Materials Science and Engineering, Shandong University of Technology, Zibo, 255000, China.

Recently, nanoparticle-triggered in situ catalytic Fenton/Fenton-like reaction is widely explored for tumor-specific chemodynamic therapy (CDT). However, despite the great potential of CDT in tumor treatment, insensitive response to the relatively high pH of the tumor sites and the insufficient intratumoral H O level leads to limited efficiency of most Fenton/Fenton-like reactions, which greatly imped its clinical conversion. This paper reports the fabrication of Fenton-type bimetallic peroxides for ultrasensitive chemodynamic therapy with high pH-activated, synergistic effect/H O self-supply-mediated cascade Fenton chemistry for the first time. The observations reveal that these bimetallic peroxides exhibit an ultrasensitive acid-activated decomposition-mediated Fenton-like reaction at the relatively high pH of 6.5-7.0, accompanied with highly increased •OH generation efficiency (especially, 40-60-fold increase at pH 7.0) by the metal-mediated synergistic effect-enhanced Fenton chemistry as well as in situ self-generated H O supplement. Moreover, the bimetallic peroxides exhibit high tumor accumulation which along with a high-efficiency tumor catalytic-therapeutic with negligible side effects in vivo. Developing these novel bimetallic peroxides, together with the already demonstrated capacity of the key metals (Fe, Mn, Cu, etc.) for magnetic resonance imaging or photodynamic/immune-enhanced therapy, will propel interest in development of smart high-efficiency nanoplatform for cancer theranostics.
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http://dx.doi.org/10.1002/adhm.202002126DOI Listing
May 2021

A green rust-coated expanded perlite particle electrode-based adsorption coupling with the three-dimensional electrokinetics that enhances hexavalent chromium removal.

Ecotoxicol Environ Saf 2021 Apr 12;213:112003. Epub 2021 Feb 12.

School of Chemistry and Materials Engineering, Changshu Institute of Technology, No. 99, South 3rd Ring Road, Changshu 215500, China.

A green rust-coated expanded perlite (GR-coated Exp-p) microelectrode was synthesized and incorporated into a column-mode three-dimensional electrokinetic (3D-EK) platform to effectively pursue a continuous Cr(VI) removal from the aqueous solution. Brucite-like layers of GR were decorated onto the Exp-p material. The molar ratio of Fe(II) to Fe(III) played a most vital role among the three synthesis factors in influencing the performance of the particle electrode. For the equilibrium adsorption experiments, the target maximum adsorption capacity of 122 mg/g was predicted by a target optimizer and desirability function at the conditions following the pH of 4.7, the initial concentration of 172.4 mg/L, the dosage of 0.28 g/L, and the temperature of 28.96 °C, respectively. SO, Cl, and NO fiercely competed with Cr(VI) anions in the acidic conditions for the locally positive sites. A low concentration and a slow flow were favored in the column-mode 3D-EK platform. The pseudo-first-order and Langmuir models were suitable for describing the kinetics and isotherms of the adsorption process, respectively. Cr(VI) anions were electrostatically attracted to the silanol groups and GR surface of the adsorbent, subsequently reduced in both heterogeneity and homogeneity, and finally immobilized by coordinating with silanediol groups and silanetriol groups.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112003DOI Listing
April 2021

Identification of inhibitors of UDP-galactopyranose mutase combinatorial screening.

Org Biomol Chem 2021 03;19(8):1818-1826

Department of Chemistry, University of Namur, Rue de Bruxelles 61, 5000 Namur, Belgium.

An in situ screening assay for UDP-galactopyranose mutase (UGM, an essential enzyme of M. tuberculosis cell wall biosynthesis) has been developed to discover novel UGM inhibitors. The approach is based on the amide-forming reaction of an amino acid core with various cinnamic acids, followed by a direct fluorescence polarization assay to identify the best UGM binders without isolation and purification of the screened ligands. This assay allows us to perform one-pot high-throughput synthesis and screening of enzyme inhibitors in a 384-well plate format. UGM ligands were successfully identified by this technology and their inhibition levels were established from pure synthetic compounds in vitro and in a whole cell antibacterial assay. This study provides a blueprint for designing enamide structures as new UGM inhibitors and anti-mycobacterial agents.
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http://dx.doi.org/10.1039/d1ob00138hDOI Listing
March 2021

A novel approach of ultrasound-guided laminar block for rib fracture surgery.

J Clin Anesth 2021 Jun 6;70:110191. Epub 2021 Feb 6.

Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.jclinane.2021.110191DOI Listing
June 2021

DNA damage response inhibitors: An avenue for TNBC treatment.

Biochim Biophys Acta Rev Cancer 2021 Apr 5;1875(2):188521. Epub 2021 Feb 5.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

The DNA damage response (DDR) is critical for the maintenance of genomic stability by sensing DNA damage, regulating cell cycle and initiating DNA repair. Drugs targeting DDR pathways have been increasingly exploited in treating various tumors. Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive tumor with constitutive activation of oncogenes, inducing replication stress and DNA damage, which require the DDR for survival. In addition, emerging studies have demonstrated that TNBC harbors aberrant genetic alterations in DDR pathways, such as a high frequency of p53 dysfunction and BRCA1/2 mutations. DDR alterations force TNBC to rely on the existing DDR pathways for survival, and make TNBC particularly sensitive to specific DDR inhibitors, such as high sensitivity of TNBC with BRCA1/2 mutations to PARP inhibitors. This review first and comprehensively covers the current status of the development of DDR inhibitors and discusses the mechanism of targeting the DDR in TNBC. Preclinical and clinical studies on inhibitors of the ATR-CHK1-WEE1 pathway and PARP inhibitors, the most studied inhibitors, and some other DDR inhibitors as monotherapy or combination therapy in TNBC are summarized. We also highlight the possible predictive biomarkers for these DDR inhibitors and their potential combination strategies with chemotherapy, radiotherapy or other targeted agents to optimize the efficacy of DDR inhibitors in TNBC treatment. In conclusion, this review discussed the recent considerations related to the use of DDR inhibitors for TNBC and provides a perspective to address future directions and potential therapeutic strategies for patients with TNBC.
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http://dx.doi.org/10.1016/j.bbcan.2021.188521DOI Listing
April 2021